Abstract
Polysaccharopeptide (PSP), from Coriolus versicolor, has been used widely as an adjuvant to chemotherapy with demonstrated anti-tumor and broad immunomodulating effects. While PSP’s mechanism of action still remains unknown, its enhanced immunomodulatory potential with acacia gum is of great interest. Acacia gum, which also contains polysaccharides and glycoproteins, has been demonstrated to be immunopotentiating. To elucidate whether PSP directly activates T-cell-dependent B-cell responses in vivo, we used a well-established hapten carrier system (Nitrophenyl-chicken gamma globulin (NP-CGG)). 6-week C57BL/6 male mice were immunised with 50 μg of NP25-CGG alum precipitate intraperitoneally. Mice were gavaged daily with 50mg/kg PSP in a vehicle containing acacia gum and sacrificed at days 0, 4, 7, 10, 14 and 21. ELISA was used to measure the total and relative hapten-specific anti-NP IgA, IgM and IgG titre levels compared to the controls. It was found that PSP, combined with acacia gum, significantly increased total IgG titre levels at day 4 (P< 0.05), decreased IgM titre levels at days 4 and 21 (P< 0.05) with no alterations observed in the IgA or IgE titre levels at any of the time points measured. Our results suggest that while PSP combined with acacia gum appears to exert weak immunological effects through specific T-cell dependent B-cell responses, they are likely to be broad and non-specific which supports the current literature on PSP. We report for the first time the application of a well-established hapten-carrier system that can be used to characterise and delineate specific T-cell dependent B-cell responses of potential immunomodulatory glycoprotein-based herbal medicines combinations in vivo.
Highlights
Evading immune destruction has been deemed as an emerging hallmark of cancer [1]
Our results suggest that while PSP combined with acacia gum appears to exert weak immunological effects through specific T-cell dependent B-cell responses, they are likely to be broad and non-specific which supports the current literature on PSP
As PSP and Acacia are both known to be immunopotentiators, it is plausible that any enhanced immune responses caused by these agents in the NP-CGG model are likely to occur in the spleen and be reflected in changes in spleen weight
Summary
Evading immune destruction has been deemed as an emerging hallmark of cancer [1]. In particular, the absence of strong cancer antigens, loss of MHC class I, or stimulatory and or costimulatory molecules can result in the failure of T-cell recognition, antigen presentation and tumor elimination [2,3]. Immunotherapy with other interleukins such as high dose IL-2 remains to be an effective treatment for the last 20 years in patients with metastatic renal cell carcinoma, conferring well-documented complete durable responses in 10–15% of select patients [8] Antibody mediated therapies such as the development of monoclonal antibodies have been used to successfully target various receptors including VEGF, EGFR, Her-2 exerting various effects on different cancers resulting in prolonged survival [9]. The aim is to develop and combine various therapeutic strategies together that deliver broad spectrum effects with potentially less toxicity while minimizing resistance, thereby improving treatment outcomes for those with cancer Thalidomide is one such drug used for the effective management of multiple myeloma, possessing complex but multifaceted effects including potent cytotoxic and immunomodulatory activities [12]. Thalidomide has the ability to stimulate prognostically significant cytotoxic T-cells responses in patients with multiple myeloma [13] and Waldenström macroglobulinemia [14]
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